Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment
A series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, ch...
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MDPI AG
2018-07-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/8/1859 |
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doaj-226896cb152a4aaaa6e17cb7eef62ac72020-11-25T01:08:07ZengMDPI AGMolecules1420-30492018-07-01238185910.3390/molecules23081859molecules23081859Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil RecruitmentJaqueline P. Januario0Thiago B. de Souza1Stefânia N. Lavorato2Tatiane C. S. Maiolini3Olívia S. Domingos4João L. Baldim5Laís R. S. Folquitto6Marisi G. Soares7Daniela A. Chagas-Paula8Danielle F. Dias9Marcelo H. dos Santos10Chemistry Institute, Federal University of Alfenas, UNIFAL-MG, Alfenas 37130-001, Minas Gerais, BrazilDepartment of Industrial Pharmacy, Federal University of Santa Maria, UFSM, Santa Maria 97105-900, Rio Grande do Sul, BrazilCenter of Biological Sciences and Health, Federal University of Western Bahia, UFOB, Barreiras 47808-021, Bahia, BrazilChemistry Institute, Federal University of Alfenas, UNIFAL-MG, Alfenas 37130-001, Minas Gerais, BrazilChemistry Institute, Federal University of Alfenas, UNIFAL-MG, Alfenas 37130-001, Minas Gerais, BrazilChemistry Institute, Federal University of Alfenas, UNIFAL-MG, Alfenas 37130-001, Minas Gerais, BrazilChemistry Institute, Federal University of Alfenas, UNIFAL-MG, Alfenas 37130-001, Minas Gerais, BrazilChemistry Institute, Federal University of Alfenas, UNIFAL-MG, Alfenas 37130-001, Minas Gerais, BrazilChemistry Institute, Federal University of Alfenas, UNIFAL-MG, Alfenas 37130-001, Minas Gerais, BrazilChemistry Institute, Federal University of Alfenas, UNIFAL-MG, Alfenas 37130-001, Minas Gerais, BrazilDepartment of Chemistry, Federal University of Viçosa, UFV, Viçosa 36570-900, Minas Gerais, BrazilA series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, characterized, and evaluated for their anti-inflammatory properties by the croton oil-induced ear edema assay to examine their effect on both prostaglandin (PG) production and neutrophils recruitment. The thiazole derivatives displayed a potent effect in terms of reducing ear edema. The analysis suggested that the presence of 4-phenyl-2-hydrazinothiazole and the absence of C4′-OCH3 on the benzophenone derivative structure are strongly related to the inhibition of PG production. In addition, the derivatives 2e, 3a and 3c concomitantly inhibit PG production and neutrophil recruitment, which may be a mechanism of action better than of common NSAIDs due to their inability to inhibit the neutrophil recruitment. Thus, these compounds can be considered as potential lead compounds toward the development of new anti-inflammatory drugs with an innovating mechanism of action.http://www.mdpi.com/1420-3049/23/8/1859hydrazinothiazoletiosemicarbazonemolecular dockingstructure activity relationshipear edema |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jaqueline P. Januario Thiago B. de Souza Stefânia N. Lavorato Tatiane C. S. Maiolini Olívia S. Domingos João L. Baldim Laís R. S. Folquitto Marisi G. Soares Daniela A. Chagas-Paula Danielle F. Dias Marcelo H. dos Santos |
| spellingShingle |
Jaqueline P. Januario Thiago B. de Souza Stefânia N. Lavorato Tatiane C. S. Maiolini Olívia S. Domingos João L. Baldim Laís R. S. Folquitto Marisi G. Soares Daniela A. Chagas-Paula Danielle F. Dias Marcelo H. dos Santos Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment Molecules hydrazinothiazole tiosemicarbazone molecular docking structure activity relationship ear edema |
| author_facet |
Jaqueline P. Januario Thiago B. de Souza Stefânia N. Lavorato Tatiane C. S. Maiolini Olívia S. Domingos João L. Baldim Laís R. S. Folquitto Marisi G. Soares Daniela A. Chagas-Paula Danielle F. Dias Marcelo H. dos Santos |
| author_sort |
Jaqueline P. Januario |
| title |
Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment |
| title_short |
Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment |
| title_full |
Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment |
| title_fullStr |
Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment |
| title_full_unstemmed |
Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment |
| title_sort |
design and synthesis of new benzophenone derivatives with in vivo anti-inflammatory activity through dual inhibition of edema and neutrophil recruitment |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2018-07-01 |
| description |
A series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, characterized, and evaluated for their anti-inflammatory properties by the croton oil-induced ear edema assay to examine their effect on both prostaglandin (PG) production and neutrophils recruitment. The thiazole derivatives displayed a potent effect in terms of reducing ear edema. The analysis suggested that the presence of 4-phenyl-2-hydrazinothiazole and the absence of C4′-OCH3 on the benzophenone derivative structure are strongly related to the inhibition of PG production. In addition, the derivatives 2e, 3a and 3c concomitantly inhibit PG production and neutrophil recruitment, which may be a mechanism of action better than of common NSAIDs due to their inability to inhibit the neutrophil recruitment. Thus, these compounds can be considered as potential lead compounds toward the development of new anti-inflammatory drugs with an innovating mechanism of action. |
| topic |
hydrazinothiazole tiosemicarbazone molecular docking structure activity relationship ear edema |
| url |
http://www.mdpi.com/1420-3049/23/8/1859 |
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